We propose to isolate and purify histone and non-histone proteins of chromatin from normal human colon and colon carcinoma tissues and from 3T3 cells and their SV40-transformed counterparts. We plan also to isolate and purify the protein kinases from nuclei of these cells and to characterize them in terms of substrate specificity, cyclic nucleotide effects, and kinetic parameters. We will seek correlations between patterns of nuclear protein phosphorylation in these tissues and the levels and substrate specificities of the purified protein kinases with the goal of locating neoplasia-related alterations in this regulatory system.